Neuropsychiatric manifestations of Systemic Lupus Erythematosus (NPSLE) are both common and an important source of morbidity. Of the case definitions for NPSLE syndromes that have recently been developed, cognitive dysfunction appears to be the most prevalent. Little is known about the influence of co-morbidities or ethnicity/race on disease outcomes or the underlying biological basis for this important NPSLE syndrome. Perhaps most importantly, no rational therapeutic approach for the treatment of SLE-related cognitive dysfunction currently exists and is unlikely to be developed without a better understanding of disease mechanisms. New brain imaging techniques have great potential to uncover mechanisms underlying NPSLE syndromes, particularly if specific syndromes are targeted. Brain imaging and the evaluation of prospectively measured biomarkers will also help determine factors that are relevant to NPSLE manifestations and may help distinguish reversible from irreversible processes. We propose to study 100 newly diagnosed patients with SLE from 10 sites for the development of cognitive dysfunction, determined using both repeatable computerized and traditional neuropsychological tests. We will prospectively evaluate the relationship of structural and functional brain imaging (using anatomic magnetic resonance imaging and resting FDG-PET), several relevant biomarkers (antiphospholipid antibodies, cytokines and adhesion molecules) and co-morbidities (race/ethnicity, depression, fibromyalgia and corticosteroid use) to cognitive dysfunction. We will also determine the impact of cognitive dysfunction on quality of life. Factors distinguishing transient or reversible versus irreversible cognitive dysfunction will be determined using a repeated measures analysis approach. The ability to study the relationship between changes in cognitive functioning and these other variables in a group of newly diagnosed SLE patients is crucial to the successful discovery of early pathologic changes that could be potentially amenable to disease-reversing therapies.